Abstract Substance use is associated with increased risk of, progression to, and negative outcomes from chronic disease. Although associations between substance use disorders (SUDs) and chronic disease are well documented, specific mechanisms underlying these associations are poorly understood and underappreciated. Experimental studies that use placebo-controlled, randomized designs are essential for understanding physiological mechanisms that link SUDs and chronic disease. The research and pilot projects in the Center for Addiction and Disease Risk Exacerbation (CADRE) COBRE at Brown University will investigate physiological mechanisms underlying the effects of opioids, cannabis, tobacco, and alcohol on risks for and progression of SUD-related disease. Mechanisms to be studied in the initial four CADRE research projects include systemic inflammation, immune system dysregulation, high blood pressure, pulmonary effects and carcinogen exposure. The CADRE's Clinical Laboratory Core (CLC) will provide the current and future CADRE research and pilot project investigators with the space, supplies, equipment, technical capability, scientific expertise and data management/analysis expertise necessary to meet the needs of their projects. These resources are not otherwise available at Brown, and are essential for achieving the Specific Aims of the CADRE projects. Provision of these resources via the CLC will improve efficiency, consistency and economy of scale across projects. Specific Aim 1 of the CLC Core is to provide resources necessary for developing and sustaining a multi-disciplinary center focused on SUDs and chronic disease. Specific Aim 2 is to facilitate and coordinate assay and other services provided to the CADRE investigators through neighboring COBREs. Specific Aim 3, an exploratory aim, is to build a center-wide biobank and database of biological, behavioral and environmental risk factors associated with the development and progression of SUDs and chronic disease. Resources provided by the CLC will build on and complement, but not overlap, resources currently available at Brown. The successful achievement of these aims will be a thematically- and technically-linked center that supports the initial and future projects, enhances the competitiveness of the project leaders for independent external funding, becomes a national leader in understanding biobehavioral mechanisms linking SUDs and chronic disease, and serves as a resource for training and research within Brown, regionally, and nationally.